The action potential duration (APD) of isolated guinea pig papillary muscle is directly related to the medium glucose concentration regardless of the gas mixture with which it is in equilibrium. The APD can be maintained at control value for many hours by a glucose concentration of 50 mM in the complete absence of oxygen. Following reduction of the APD by incubation of the muscle in medium containing 5 mM glucose, adjustment of the glucose concentration to 50 mM will cause restoration of normal APD. Phlorizin has been shown to competitively interfere with the effect of glucose on the APD and insulin to prevent or reverse the effect of phlorizin. Nonmetabolizable sugars cannot produce glucose-like effects on the APD. Adrenaline, noradrenaline, and isopropylnoradrenaline increased the reduced APD of papillary muscles incubated in the absence of oxygen in a medium containing 5 mM glucose coincident with an increase in contractile force. The effect of isopropylnoradrenaline was blocked by acetylcholine and propranolol. In the presence of iodoacetate and 2-deoxyglucose, isopropylnoradrenaline increased contractile force but not the reduced APD. Aminophylline was found to produce changes in the reduced APD similar to those caused by the sympathomimetic amines. The findings clearly support the hypothesis that anaerobic metabolism utilizing either glycogen or exogenous glucose is capable of maintaining normal transmembrane electrical activity in guinea pig papillary muscle.